Threonine epimerization

Zur Benennung der Epimere der physiologisch vorkommenden Aminosauren mit zwei Chiralitatszentren gibt es eine besondere Vor-silbe, namlich die Vorsilbe Alio-. Demnach heifien die Epimere von Threonin und Isoleucin Allothreonin bzw. Alloisoleucin. 

This enzyme s role in humans is to assist the detoxification of propionate derived from the degradation of the amino acids methionine, threonine, valine, and isoleucine. Propionyl-CoA is carboxylated to (5 )-methylmalonyl-CoA, which is epimerized to the (i )-isomer. Coenzyme Bi2-dependent methylmalonyl-CoA mutase isomerizes the latter to succinyl-CoA (Fig. 2), which enters the Krebs cycle. Methylmalonyl-CoA mutase was the first coenzyme B -dependent enzyme to be characterized crystallographically (by Philip Evans and Peter Leadlay). A mechanism for the catalytic reaction based on ab initio molecular orbital calculations invoked a partial protonation of the oxygen atom of the substrate thioester carbonyl group that facilitated formation of an oxycyclopropyl intermediate, which connects the substrate-derived and product-related radicals (14). The partial protonation was supposed to be provided by the hydrogen bonding of this carbonyl to His 244, which was inferred from the crystal structure of the protein. The ability of the substrate and product radicals to interconvert even in the absence of the enzyme was demonstrated by model studies (15). 

In addition to these crucial domains, other modifying domains are often found in NRPS modules. These include heterocyclization domains, which catalyze the formation of heterocyclic rings from cysteine, serine, and threonine residues (see Section 2.06.2). Epimerization domains are structurally very similar to condensation... 

Figure 10 Deacetylation of the 3-mer model O-glycopeptide did not cause -elimination or epimerization of threonine.

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